Aging-Associated Changes in Oxidative Stress Negatively Impacts the Urinary Bladder Urothelium.
Aging-Associated Changes in Oxidative Stress Negatively Impacts the Urinary Bladder Urothelium.
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DOI：
10.5213/inj.2142224.112
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发表时间：
2022-06
影响因子：
2.3
通讯作者：
Birder, Lori A.
中科院分区：
文献类型：
--
作者：
de Rijk, Mathijs M.;Wolf-Johnston, Amanda;Kullmann, Aura F.;Taiclet, Stephanie;Kanai, Anthony J.;Shiva, Sruti;Birder, Lori A.
已知下尿路症状会随着年龄的增长而显著增加，对生活质量和自力更生产生负面影响。尿道鞘完成关键任务，作为保护下方膀胱组织免受尿液的苛刻化学成分影响的屏障，并通过膀胱壁内影响膀胱功能的介质的释放表现出信号传导特性。衰老与细胞健康的有害变化有关，部分是通过增加膀胱粘膜，更具体地说是膀胱粘膜中的氧化应激。这反过来可能会影响尿路上皮线粒体健康和生物能量学。我们收集了年轻（3-4个月大）和老年（25-30个月大）大鼠的粘膜组织样本。通过蛋白质免疫印迹法评价组织的p21-Arc、硝基酪氨酸和细胞色素C表达。培养尿路上皮细胞进行单细胞成像，以分析活性氧和线粒体膜电位的基础水平。线粒体的生物能量学和细胞呼吸进行了研究海马测定，并测量腺苷三磷酸释放的荧光素酶测定。衰老与细胞衰老、氧化应激和基础活性氧水平的生物标志物显著增加相关。在老年动物的尿路上皮细胞培养物中，线粒体膜电位显著降低，老年动物的培养物显示线粒体生物能量学显著降低。与年龄相关的氧化应激和过量活性氧的增加可能是老年人下尿路症状的潜在因素。本研究中概述的机制可用于确定新的药物靶点，以改善衰老相关的膀胱功能障碍。
Lower urinary tract symptoms are known to significantly increase with age, negatively impacting quality of life and self-reliance. The urothelium fulfills crucial tasks, serving as a barrier protecting the underlying bladder tissue from the harsh chemical composition of urine, and exhibits signaling properties via the release of mediators within the bladder wall that affect bladder functioning. Aging is associated with detrimental changes in cellular health, in part by increasing oxidative stress in the bladder mucosa, and more specifically the urothelium. This, in turn, may impact urothelial mitochondrial health and bioenergetics. We collected mucosal tissue samples from both young (3–4 months old) and aged (25–30 months old) rats. Tissue was evaluated for p21-Arc, nitrotyrosine, and cytochrome C expression by western immunoblotting. Urothelial cells were cultured for single-cell imaging to analyze basal levels of reactive oxygen species and the mitochondrial membrane potential. Mitochondrial bioenergetics and cellular respiration were investigated by the Seahorse assay, and measurements of adenosine triphosphate release were made using the luciferin-luciferase assay. Aging was associated with a significant increase in biomarkers of cellular senescence, oxidative stress, and basal levels of reactive oxygen species. The mitochondrial membrane potential was significantly lower in urothelial cell cultures from aged animals, and cultures from aged animals showed a significant decrease in mitochondrial bioenergetics. Aging-related increases in oxidative stress and excessive reactive oxygen species may be contributing factors underlying lower urinary tract symptoms in older adults. The mechanisms outlined in this study could be utilized to identify novel pharmaceutical targets to improve aging-associated bladder dysfunction.
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影响因子：
2.6
作者：
Birder LA;Kullmann AF;Chapple CR
通讯作者：
Chapple CR
影响因子：
6.1
作者：
Hanna-Mitchell, Ann T.;Beckel, Jonathan M.;Birder, Lori A.
通讯作者：
Birder, Lori A.
影响因子：
2.1
作者：
Shie, Jia-Heng;Liu, Hsin-Tzu;Kuo, Hann-Chorng
通讯作者：
Kuo, Hann-Chorng
影响因子：
23.4
作者：
Irwin, Debra E.;Milsom, Ian;Abrams, Paul
通讯作者：
Abrams, Paul
影响因子：
5.5
作者：
Ferguson, DR;Kennedy, I;Burton, TJ
通讯作者：
Burton, TJ